Regius, aka Hendrik de Roy, was born at Utrecht, the son of a wealthy family of brewers. After studying law and medicine at Franeker, Groningen, and Leiden, he studied at the universities of Paris, Montpellier, and Padua, where he also took his degree (1623). Back in Utrecht, he became town physician (a honorary position for the care of the poor and the instruction of surgeons). After a short interval as principal of the Latin School at Naarden (1630–34), he returned to Utrecht and resumed his duties as town physician. Descartes’ Discourse on Method (1637), and especially the accompanying essays Dioptrics and Meteors, inspired him to elaborate a system of physics of his own, which he taught privately to students of the university. In 1638, after a successful lobbying campaign by Henricus Reneri, he became professor of theoretical medicine.

Regius sought contact with Descartes, to whom, as he declared in his first letter, he owed his appointment. It was the beginning of a correspondence and a friendship, which for both must have been immensely stimulating. Regius submitted draft versions of his disputations to Descartes; Descartes in turn used Regius's activities as an opportunity to test his ideas before a wider audience. Regius's vociferous opposition to traditional philosophy, however, produced tensions with his colleagues, especially the theologian Gysbertus Voetius. These escalated on December 8, 1641, when Regius had a student defend three claims that caused great alarm: the union of mind and body is “accidental” (see human being); the earth moves; and Aristotelian substantial forms must be rejected (see form, substantial). Although Voetius convinced the theological faculty that an official reaction was needed, the administration of the university achieved a compromise: it refused to condone an open condemnation of Regius but allowed Voetius to defend the traditional position and publish his apprehensions about the rejection of substantial forms. Things might have ended there, had not Regius and Descartes the idea that a public reaction was needed. A Responsio, written by Regius in collaboration with Descartes, was published in February 1642. It caused so much offense that Voetius managed to obtain an official condemnation of the new ideas. Regius lost his permission to lecture on general physics and was confined to the medical faculty.